Dr. Daniel P. Petrylak, Professor of Medicine and Urology at Yale School of Medicine, has been a pioneer in the research and development of new drugs and treatments to fight prostate, bladder, kidney, and testicular cancers.
Prostatepedia spoke with him about newer combinations with Xofigo.
Dr. Petrylak: Xofigo (radium-223) can be very useful in patients. The prevailing wisdom in the past has been to only give isotopes late in the course of the disease because drugs like strontium and samarium had only palliative effects. There was also concern that strontium and samarium could cause prolonged myelosuppression (bone marrow suppression) in patients. Patients who are treated early in the course of their disease with strontium and samarium may have difficulty receiving subsequent chemotherapy.
Xofigo (radium-223) has an advantage over both strontium and samarium in that it is an alpha particle rather than a beta particle. The alpha particle will induce double-stranded DNA breaks as opposed to the beta particle’s single-stranded breaks. Double-stranded DNA breaks cause much more DNA damage in the tumor cells; it is much more difficult for the body to repair that damage.
The alpha particle’s other advantage is that it has a short nucleus, or radius of activity. It spares normal marrow and will hopefully cause less myelosuppression.
Xofigo (radium-223) has a survival benefit. It is approved for either pre- or post-chemotherapy.
There are a couple of interesting observations being made that will hopefully be confirmed in randomized trials. If you look at Xofigo’s (radium-223) expanded access protocol, there does appear to be better survival when you combine Xofigo (radium-223) with Zytiga (abiraterone). There is also better survival when you combine Xofigo (radium-223) with Xgeva (denosumab).
Combinations give you more bang for your buck. Randomized trials are now evaluating these combinations. I think there is great promise in these combinations. We all know that there is an interaction between hormones and radiation therapy. Giving the two together is very interesting.
The immune question is an important one. We have some data that we’re submitting for publication that shows that there is upregulation of PD-L1 on immune cells after patients receive Xofigo (radium-223). The question is: does that make the patients more sensitive to subsequent immune therapy?
There are clinical trials looking at combinations of Keytruda (pembrolizumab) plus Xofigo (radium-223), vaccine therapy plus Xofigo (radium-223), atezoluzimab plus Xofigo (radium-223) and Provenge (sipuleucel-T) plus Xofigo (radium-223) This is an important venue for trying to synergize between different treatments.